Criticality of Surface Characteristics of Intravenous Iron–Carbohydrate Nanoparticle Complexes: Implications for Pharmacokinetics and Pharmacodynamics
Un-complexed polynuclear ferric oxyhydroxide cannot be administered safely or effectively to patients. When polynuclear iron cores are formed with carbohydrates of various structures, stable complexes with surface carbohydrates driven by multiple interacting sites and forces are formed. These comple...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/4/2140 |
| _version_ | 1797479312829448192 |
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| author | Felix Funk Beat Flühmann Amy E. Barton |
| author_facet | Felix Funk Beat Flühmann Amy E. Barton |
| author_sort | Felix Funk |
| collection | DOAJ |
| description | Un-complexed polynuclear ferric oxyhydroxide cannot be administered safely or effectively to patients. When polynuclear iron cores are formed with carbohydrates of various structures, stable complexes with surface carbohydrates driven by multiple interacting sites and forces are formed. These complexes deliver iron in a usable form to the body while avoiding the serious adverse effects of un-complexed forms of iron, such as polynuclear ferric oxyhydroxide. The rate and extent of plasma clearance and tissue biodistribution is variable among the commercially available iron–carbohydrate complexes and is driven principally by the surface characteristics of the complexes which dictate macrophage opsonization. The surface chemistry differences between the iron–carbohydrate complexes results in significant differences in in vivo pharmacokinetic and pharmacodynamic profiles as well as adverse event profiles, demonstrating that the entire iron–carbohydrate complex furnishes the pharmacologic action for these complex products. Currently available physicochemical characterization methods have limitations in biorelevant matrices resulting in challenges in defining critical quality attributes for surface characteristics for this class of complex nanomedicines. |
| first_indexed | 2024-03-09T21:44:59Z |
| format | Article |
| id | doaj.art-62f4cddf7b844981a3f6e5954e10da6e |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T21:44:59Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-62f4cddf7b844981a3f6e5954e10da6e2023-11-23T20:20:41ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-02-01234214010.3390/ijms23042140Criticality of Surface Characteristics of Intravenous Iron–Carbohydrate Nanoparticle Complexes: Implications for Pharmacokinetics and PharmacodynamicsFelix Funk0Beat Flühmann1Amy E. Barton2Vifor Pharma Management Ltd., Flughofstrasse 61, CH-8152 Glattbrugg, SwitzerlandVifor Pharma Management Ltd., Flughofstrasse 61, CH-8152 Glattbrugg, SwitzerlandVifor Pharma Management Ltd., Flughofstrasse 61, CH-8152 Glattbrugg, SwitzerlandUn-complexed polynuclear ferric oxyhydroxide cannot be administered safely or effectively to patients. When polynuclear iron cores are formed with carbohydrates of various structures, stable complexes with surface carbohydrates driven by multiple interacting sites and forces are formed. These complexes deliver iron in a usable form to the body while avoiding the serious adverse effects of un-complexed forms of iron, such as polynuclear ferric oxyhydroxide. The rate and extent of plasma clearance and tissue biodistribution is variable among the commercially available iron–carbohydrate complexes and is driven principally by the surface characteristics of the complexes which dictate macrophage opsonization. The surface chemistry differences between the iron–carbohydrate complexes results in significant differences in in vivo pharmacokinetic and pharmacodynamic profiles as well as adverse event profiles, demonstrating that the entire iron–carbohydrate complex furnishes the pharmacologic action for these complex products. Currently available physicochemical characterization methods have limitations in biorelevant matrices resulting in challenges in defining critical quality attributes for surface characteristics for this class of complex nanomedicines.https://www.mdpi.com/1422-0067/23/4/2140nanomedicineiron–carbohydrate complexescarbohydrate |
| spellingShingle | Felix Funk Beat Flühmann Amy E. Barton Criticality of Surface Characteristics of Intravenous Iron–Carbohydrate Nanoparticle Complexes: Implications for Pharmacokinetics and Pharmacodynamics International Journal of Molecular Sciences nanomedicine iron–carbohydrate complexes carbohydrate |
| title | Criticality of Surface Characteristics of Intravenous Iron–Carbohydrate Nanoparticle Complexes: Implications for Pharmacokinetics and Pharmacodynamics |
| title_full | Criticality of Surface Characteristics of Intravenous Iron–Carbohydrate Nanoparticle Complexes: Implications for Pharmacokinetics and Pharmacodynamics |
| title_fullStr | Criticality of Surface Characteristics of Intravenous Iron–Carbohydrate Nanoparticle Complexes: Implications for Pharmacokinetics and Pharmacodynamics |
| title_full_unstemmed | Criticality of Surface Characteristics of Intravenous Iron–Carbohydrate Nanoparticle Complexes: Implications for Pharmacokinetics and Pharmacodynamics |
| title_short | Criticality of Surface Characteristics of Intravenous Iron–Carbohydrate Nanoparticle Complexes: Implications for Pharmacokinetics and Pharmacodynamics |
| title_sort | criticality of surface characteristics of intravenous iron carbohydrate nanoparticle complexes implications for pharmacokinetics and pharmacodynamics |
| topic | nanomedicine iron–carbohydrate complexes carbohydrate |
| url | https://www.mdpi.com/1422-0067/23/4/2140 |
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